title: Luteolin induces growth arrest in colon cancer cells through involvement of Wnt/β-catenin/GSK-3β signaling.
abstract: Cancer is a multistep process that typically occurrs over an extended period of time, beginning with initiation followed by promotion and progression. Colon cancer is the leading cause of morbidity and mortality worldwide. For a variety of reasons, patients prefer naturally occurring dietary substances over synthetic agents to prevent cancer. Luteolin, a bioflavonoid, possesses antioxidant, anti-inflammatory, and antiproliferative effects. We analyzed the in vitro anticancer and apoptosis-inducing property of luteolin using HCT-15 colon adenocarcinoma cells. Cell viability was assessed using trypan blue assay at different concentrations. Luteolin at a concentration of 100 µM (IC50) decreased the expressions of non-P-β-catenin, phosphorylated (inactive) glycogen synthase kinase-3β, and cyclin D1 expressions in HCT-15 cells, which were confirmed by Western blot analysis. Luteolin also promoted substantial cell cycle arrest at the G2/M phase in HCT-15 cells, and it induces apoptosis in HCT-15 cells, as revealed by flow cytometric analysis. Furthermore, Western blot analysis showed that luteolin treatment enhanced the expression of Bax and caspase-3, whereas the expression of Bcl-2 was suppressed. Together, the results of this study revealed that luteolin can act as a potent inhibitor of HCT-15 proliferation and can be used as an agent against colon cancer.
authors.affiliation: Department of Biochemistry, Cell Biology Lab, University of Madras, Guindy Campus, Chennai, India.
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Pandurangan
authors.forename: Prakash
authors.initials: P
authors.lastname: Dharmalingam
authors.forename: Suresh Kumar Ananda
authors.initials: SK
authors.lastname: Sadagopan
authors.forename: Manikandan
authors.initials: M
authors.lastname: Ramar
authors.forename: Arumugam
authors.initials: A
authors.lastname: Munusamy
authors.forename: Sudhandiran
authors.initials: S
authors.lastname: Ganapasam
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D047311:Luteolin / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; C530104:CCND1 protein, human; C495270:CTNNB1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051176:beta Catenin; D019938:Cyclin D1; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D053148:Caspase 3; D047311:Luteolin